The human multipotential stem cell line K-562 is an excellent model for the study of cell differentiation in human leukemia cells. This cell line was originally established at our laboratory with blasts from a patient with chronic myelocytic leukemia (CML) in terminal blast crisis. The original line has been maintained in serial culture for 14 years and many sublines have been derived from samples of cells frozen at various passages. The K-562 cells are highly undifferentiated blasts with the potential for differentiation along the erythrocytic, granulocytic, monocytic, lymphocytic, and megakaryocytic cell lineages. Each subline has characteristic chromosomal aberrations and antigenic expression for a variety of hematopoietic differentiation antigens. The specific aims of this project are: 1) to study the morphologic features and changes in antigenic expression induced by biological response modifiers or inducers of cell differentiation such as hemin, dimethysulfoxide, retinoic acid, DNA inhibitors, growth factors, interleukins 1 and 2 and specific antibodies; 2) to assess if the K-562 cells lose their characteristic malignancy at some stage of differentiation and maturation; 3) to investigate correlations between specific chromosome aberrations and the response of the cells to various inducers; and 4) to study the relationship between oncogene activation at the breaking points of chromosomal aberrations and the potential for differentiation of different sublines. The results of the studies will help elucidate the mechanism involved in the arrest of cell differentiation present in highly malignant blasts. This information will increase our understanding on how malignant cells can be induced to differentiate and to stop or reduce their active proliferation. The long term goal is to develop new therapeutic modalities for myelogenous, lymphoid or erythroid types of human leukemia. (M)